Bone disorders such as osteoarthritis (OA) and osteoporosis are responsible for a large global economic burden. OA alone affects approximately 27 million adults in the United States. OA is a chronic condition that is usually diagnosed at a late stage when the only treatment options are total joint replacement surgery or palliative treatments. Regardless of whether the cause of OA is cartilage, bone, or both, early diagnosis is of vital importance in planning treatment. Meanwhile, osteoporosis affects 44 million people age 50 or older in the United States alone. Other conditions including, but not limited to, bone fracture, Paget's disease, osteolytic tumors, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, osteopenia (including drug-induced osteopenia), and hypercalcemia, also cause loss of bone mass and affect hundreds of millions of people worldwide.
Those suffering from these maladies are predisposed to loss of bone mass, enhanced bone fragility, and increased risk of traumatic fracture. Each condition has various etiologies such as congenital conditions, malnutrition, or risk of various additional factors. For example, osteoporosis alone has at least three etiologies. In all types, the declining ability of the bone remodeling machinery results in bone fragility. Type I or postmenopausal osteoporosis occurs in women 51-75 years of age; in this type, estrogen deficiency shifts bone remodeling to favor bone resorption over bone formation, resulting a net bone loss. Type II or senile osteoporosis affects women about twice as often as it affects men and occurs from ages 75 to 90 years. Type III or secondary osteoporosis is caused by medications, cancers, endocrine disorders, chronic liver and/or kidney disease, and other conditions.
The current gold standard for diagnosis of OA is X-ray radiography to measure the distance between the two ends of bone in a joint as an indirect measure of cartilage loss. Nonetheless, OA is characterized by altered bone remodeling during its progression. Bone remodeling in OA patients is further characterized by occurring to different degrees at different locations in the body.
It has been suggested that changes in bone happen before cartilage degeneration begins, although this idea remains controversial. Currently, nuclear medicine is able to image bone turnover after the administration of bone-targeting tracers such as 99mTc-MDP (methylene diphosphonate). However, radioisotope availability is sometimes limited, and exposure to radioisotopes carries with it some health risks, not only to the patient, but also to those who encounter the patient for a few days after treatment. Bone scintigraphy has been demonstrated to predict cartilage loss before the occurrence of radiographic changes. Alternatively, elemental strontium has been used as a calcium surrogate in high-resolution mapping of the metabolic activity of bone in osteoarthritic rats.
Magnetic resonance imaging (MRI) is a powerful diagnostic modality for imaging and assessment of cartilage, as well as inflammation-related features such as synovitis and bone marrow lesions, but is limited to structural information. The development of a contrast agent targeting bone would open the possibility for imaging bone metabolic activity via MRI while at the same time collecting structural information, simply by changing the pulse sequence. This could aid in diagnosis and treatment decisions for patients with a variety of metabolic bone disorders.